Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• sesquiterpene with a unique framework. Indeed, this natural compound has a rare [6.3.0] carbocyclic backbone with a bridging butyrolactone, and possesses five cis stereocenters [39][40]. This compound, in a racemic version, has been studied by Krafft, Cheung and Abboud (Scheme 13) [39]. The initial strategy

• displays a similar backbone as asteriscanolide (2), with an α,β-unsaturated ketone on the eight-membered ring, fused with a γ-butyrolactone and a cyclopentane, onto which a cyclopropane is also grafted [48]. The total synthesis of (±)-naupliolide (97) reported by Ito et al. constituted another example of

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• polymerization (ATRP) reactions and functional polymer synthesis [29][30][31][32][33][34]. Although α-bromo-γ-butyrolactone, which is a five-membered lactone, is easily accessible from the five-membered lactone by some bromination methods [35][36], the bromination method for the six-membered lactone, δ

• begin by first discussing the properties and stabilities of industrially important five- and six-membered lactones. γ-Butyrolactone and its α-brominated derivative are both stable at room temperature; α-bromo-γ-butyrolactone is readily synthesized by brominating the five-membered lactone under basic

• 2). 2a was obtained in 89% yield when this protocol was used on a 31 mmol scale (Table 1, entry 3). γ-Butyrolactone (1b) and ε-caprolactone (1c) were also converted into the corresponding dibromocarboxylic acids 2b and 2c in yields of 76% and 70%, respectively (Table 1, entries 4 and 5). Since we

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• observations are noted: N-Fluoro-2,6-bis(methoxymethyl)pyridinium triflate (5-4l) fluorinated the trimethylsilyl ether of γ-butyrolactone and 1-cyclohexenyl acetate in much higher yields than the N-fluoro-2,4,6-trimethyl salt 5-4j [32]. Thus, as seen in Scheme 13, 5-4l converted the Corey lactone 5-7 via its

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• 501-1193, Japan 10.3762/bjoc.16.227 Abstract New synthetic methods for spirolactams bearing an α-methylene-γ-butyrolactone or its analogous methylene-lactam have been developed. The allylation of γ-phenylthio-functionalized γ-lactams with 2-(acetoxy)methyl acrylamides was accomplished by using 2.5

• -butyrolactone; spirolactams; Introduction α-Methylene-γ-butyrolactone is a pharmaceutically important motif which is found in a wide variety of bioactive molecules including natural products (Scheme 1a) [1][2][3]. For example, sesquiterpene lactones represented by parthenolide and helenalin have attracted

• reaction conditions and led to methylene-lactone-fused spirolactams 5a–h in excellent yields without exception (88–98% two-step yields). Thus, we established the bifurcated synthetic routes toward lactams spiro-fused to α-methylene-γ-butyrolactone or α-methylene-γ-butyrolactam by using 3-phenylthiolactams

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• -bis(hydroxymethyl)indolin-2-one (51) was reacted first with mesyl chloride and then treated with sodium sulfide to afford 6-bromospiro[indoline-3,3′-thietan]-2-one (53), which was further converted into the target inhibitor candidate 54 [42] (Scheme 12). 2-Methylene-γ-butyrolactone (55) as the initial

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• traditional reactivity of this compound. Here, we investigated the possibility of applying monochloroacetic acid as a substrate for photoredox catalysis with styrene to directly produce γ-phenyl-γ-butyrolactone. Instead of using nucleophilic substitution, we cleaved the carbon chlorine bond by single-electron

• reduction, creating a radical species. We observed that the reaction works best in nonpolar solvents. The reaction does not go to full conversion, but selectively forms γ-phenyl-γ-butyrolactone and 4-chloro-4-phenylbutanoic acid. Over time the catalyst precipitates from solution (perhaps in a decomposed

• acetonitrile. Indeed, the yield decreased with increasing amounts of acetonitrile. On the other hand, the selectivity for the formation of the lactone increased by adding more acetonitrile [46]. To evaluate if γ-phenyl-γ-butyrolactone (1) can be formed from 4-chloro-4-phenylbutanoic acid (3) in benzene we

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• alkoxide anions. This reduces the occurrence of undesirable side-reactions, e.g., intermolecular aldol reaction, lactone/ketonitrile product dimerization and ring-opening polymerization. The application of this method to produce the analogous hemiketal 6 from γ-butyrolactone was not as efficient. Although

• the desired product 6 could indeed be isolated in 15% yield from γ-butyrolactone when the same reaction conditions were applied in THF, the use of 2MeTHF as solvent resulted in a complex mixture with only traces of the desired product, as revealed by crude product NMR spectroscopy. It is thought that

• be the uncyclized β-ketonitrile 7 (see Supporting Information File 1). This suggests that, in solution, the keto–hemiketal equilibrium for the butyrolactone product does not favor completely hemiketal 6, as was observed for the 6-membered cycle 5. The authors therefore propose that formation of the 6

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• dehydrogenase could oxidise the alcohol (at C-11 or C-12) to an aldehyde. Depending on whether C-11 or C-12 formed an aldehyde, further oxidation of the aldehyde to a carboxylic acid and condensation with the γ-OH group would afford the butyrolactone ring in nanagenines A–E and isonanagenines B/D, respectively

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• at the nerolidyl cation (Figure 5b) [28][29][30][31]. The biosynthesis of 1–8 and 10–11 are likely to be derived from sativene with a key oxidation at C-15 followed by a Baeyer–Villiger oxidation to break the C-14–C-15 bond (Figure 5c). Based on an isotope labelling study, the γ-butyrolactone moiety

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• disease [99]. Synthesis of enantiomerically pure (3R,5S)-168 could be accomplished from the aziridine aldehyde (2S,1'R)-6 because the butyrolactone ring formation would proceed with inversion of configuration at C2 in the aziridine ring (Scheme 43) [100]. Thus, condensation of the aldehyde (2S,1'R)-6 with

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• ]. With these issues in mind, we carried out a retrosynthetic analysis (Scheme 2) in which 10, an iodo analogue to the starting material 3, could be generated in a single step via a decarboxylative ring-opening of α-acetyl butyrolactone 8. The iodo analogue 10 could then be used without isolation to

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• -γ-butyrolactone in DMF at 130 °C [73]. This method could successfully be applied in the synthesis of the spiroketal core of rubromycins 22 and 23. One of the latest publications around the topic is published by Hayashi et al. in 2015 [74]. Starting from diarylmethylamines 24 and arylboroxines, they

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• alkylation conditions, intramolecular lactonisation of 4-bromobutyric acid to γ-butyrolactone (8) was more rapid than N-alkylation and no indolium product was observed (Scheme 4). Consequently, to obtain C4SP, we employed an optimised version of the three-step procedure of Natali et al. [3], wherein

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• low content of oligoester components were first prepared by a totally green procedure by Harada and co-workers [17]. They succeeded to polymerize a series of cyclic esters including β-butyrolactone (BL), δ-valerolactone (VL) and ε-caprolactone (CL). A recent work published by Galia et al. [18] brings

• substituted unit appear as a small broadening of the peaks for the unsubstituted units. Similar compounds (CDs esterified with δ-valerolactone, β-butyrolactone and ε-caprolactone obtained by bulk polymerization) were reported by Harada et al. and were also analyzed by 13C NMR [17]. The structural assignment

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• -bromoacetonitrile. The preparation of 3 in three steps from commercially available 3-amino-1-propanol and γ-butyrolactone (4) and its subsequent transformation into the substituted enamines is shown in Scheme 1. As described previously [28], 3-amino-1-propanol was condensed with γ-butyrolactone (4) in a sealed

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• nitro functionality (Scheme 5). Similarly, Kesavan and co-workers reacted 3-O-Boc-oxindoles 23 with MBH carbonates 22 to generate a range of spirocyclic scaffolds containing α-exo-methylene-γ-butyrolactone 24 – again using β-ICPD (Scheme 6) [30]. Nazarov cyclization An asymmetric Nazarov cyclization has

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• ] either bear a similar seco-ring fragment, as observed for dictyodiol (24), or comprise a fused γ-butyrolactone moiety, as in dictyolactone (25, Figure 3). This review intends to provide a comprehensive overview of research covering xenicane diterpenoids and related natural products. In the following

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• -methylpentanone and γ-butyrolactone), the Grubbs 2nd generation catalyst 3 performs best. In all cases, the initial ring-closing metathesis rates are highest with precatalyst 2. The same experiments were conducted with the fluorophore–quencher substrate 5 (Figure 3). In this case, the concentration of the

• : acetic acid; b: 2-methylpentanone; c: toluene; d: o-xylene; e: γ-butyrolactone; f: anisole). Fluorescence evolution resulting from closing metathesis of fluorescence–quencher substrate 5 (λexcitation = 320 nm and λemission = 400 nm). Different catalysts 1–4 (1: blue; 2: red, 3: green, 4: purple) were

• screened in different solvents (a: acetic acid; b: 2-methylpentanone; c: toluene; d: o-xylene; e: γ-butyrolactone; f: anisole). Comparison of kinetics measured by HPLC a) and by a plate reader b) for the ring-closing metathesis of 8 in acetic acid. Two profluorescent substrates yielding fluorescent

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• glucuronide 2 was found to be almost completely stable in both buffer systems over the entire temperature range. Only after heating at 90 °C in acidic buffer for 3 days could a small amount of γ-butyrolactone (GBL) be detected (Figure 3). Under forcing acidic conditions (autoclaving for 15 min with 4 M aq HCl

Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10

• Teresa Weise,
• Marco Kai,
• Anja Gummesson,
• Armin Troeger,
• Stephan von Reuß,
• Silvia Piepenborn,
• Francine Kosterka,
• Martin Sklorz,
• Ralf Zimmermann,
• Wittko Francke and
• Birgit Piechulla

Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65

• weapons against competitive fungi. As a first approach in our investigations, we analysed the profiles of its volatiles. Only two volatile organic compounds released by X. campestris have so far been described: 11-methyldodec-2Z-enoic acid [13] and γ-butyrolactone [28]. To extend this preliminary

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• tolerance make this catalytic process a promising route for the synthesis of architecturally complex polycyclic structures. Keywords: alcohol; butyrolactone; carbene; gold-catalysis; intramolecular oxaallylic alkylation; Introduction Allylic alcohols are highly desirable, readily available, cheap, and

• conditions (Table 1). Initial attempts to perform the lactonization reaction of 1a were carried out by means of a silver-free cationic complex [P(t-Bu)2o-biphenyl](AuCH3CN)SbF6 (5 mol %). The desired butyrolactone 2a was obtained selectively under reflux in DCE for 16 h (entry 1), although only in low yield

• alkylation, 1g) dppf-based species (catalytic system B) led to a complex mixture of crude reaction products (entry 7), while carbene–gold complex provided mainly the butyrolactone 2g. Moreover, the methodology proved to be tolerant toward several functional groups/atoms at the methylene carbon atom of the

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• provided directly the desired styrene 103 in good overall yield. A possible explanation for this fragmentation is outlined in Scheme 30. The enolate of ketone 104 reacts with oxygen to form the peroxide anion 105, which cleaves to give the α-keto-γ−butyrolactone 106. Treatment of the latter with aqueous

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

Stereoselective α-fluoroamide and α-fluoro- γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

• Kenny Tenza,
• Julian S. Northen,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2005, 1, No. 13, doi:10.1186/1860-5397-1-13

• fluorinated products 24 and 25 gave diastereoisomeric γ-butyrolactone products (3R, 5R)-12 and (3R, 5S)-13 and (3S, 5R)-29 and (3S, 5S)-30 respectively, each in a ratio of 10:1 as shown in Scheme 8. The 12/13 mixture had an optical rotation of ([α]D = +15°) indicating a similar absolute stereochemistry to